Lilly's $7B Kelonia Deal and CellOrigin-Walvax Program Highlight In Vivo CAR-T Momentum

Lilly plans to acquire Massachusetts-based Kelonia Therapeutics for $7 billion, with $3.25 billion paid upfront, marking the latest big pharma move into in vivo CAR-T cell therapies. At the same time, China-based CellOrigin Biotech and Walvax Biotechnology have launched an investigator-initiated clinical program evaluating an mRNA-LNP-based in vivo GPC3-targeted CAR-T therapy for hepatocellular carcinoma, one of the first disclosed Chinese clinical efforts in the emerging in vivo CAR-T field.

Kelonia's lead program, KLN-1010, is a first-in-class lentiviral in vivo CAR-T therapy in phase 1 for relapsed and refractory multiple myeloma. The engineered lentiviral-based particles are designed to selectively enter T cells inside the body, triggering the patient's body to generate CAR-T cells that target cancer cells. The therapy achieved 100% early measurable residual disease (MRD)-negative response, meaning detection tests showed no remaining cancer cells after the first month of treatment. CAR T-cell expansion peaked around day 15, and memory phenotype T cells persisted in the marrow and blood through the third month. "Autologous CAR-T therapies have meaningfully improved outcomes for patients with various cancers, but significant manufacturing, safety, and access barriers mean that only a fraction of eligible patients actually receive them," said the executive vice president and president of Lilly Oncology. "Kelonia's in vivo platform has the potential to change that by delivering rapid, durable responses in a far simpler, off-the-shelf format."

Lilly's venture into in vivo CAR-T is recent; it announced in February that it would purchase Orna Therapeutics for up to $2.4 billion. Orna's circular RNA platform uses lipid nanoparticles to deliver RNA, and its therapies are "truly off-the-shelf," generating CAR-T, CAR-NK and CAR-Mac inside the body. The pipeline is led by ORN-252, in phase 1/2 trials for B cell-driven autoimmune diseases and cancers.

For CellOrigin and Walvax, the collaboration combines CellOrigin's cell therapy design capabilities with Walvax's GMP mRNA manufacturing infrastructure, which originates from its COVID-19 vaccine program. The program's preclinical basis was presented at ASCO 2025, and CellOrigin used the ASCO 2026 meeting to present two additional solid tumor candidates: CAR-Mix, a combination of engineered macrophages and polyclonal T cells with an investigator-initiated trial underway in mesothelin-positive ovarian cancer, and TMT Engager, an LNP-mRNA-based in vivo T-cell engager designed to form tripartite conjugates between T cells, macrophages, and tumor cells.

GPC3 has become one of the leading targets in HCC cell therapy. Myeloid Therapeutics initiated first patient dosing with MT-303, a GPC3-targeting RNA CAR delivered via LNP, in a phase 1 study for advanced HCC in July 2024, and subsequently presented first-in-human in vivo mRNA CAR data at ASCO 2025. Unlike CellOrigin's approach, Myeloid's platform programs myeloid cells rather than T cells. Carisma Therapeutics, under its collaboration with Moderna, has also nominated a GPC3 in vivo CAR-macrophage development candidate for HCC.

Other big pharma deals have shaped the in vivo CAR-T space. AstraZeneca bought EsoBiotec for $1 billion in March last year, acquiring its Engineered NanoBody Lentiviral (ENaBL) platform. Gilead-owned Kite Pharma bought Interius BioTherapeutics for $350 million; Interius' in vivo CAR-T therapy INT2104 was the first of its kind to hit the clinic in Europe.